tbuckley/cabot-search huggingface dataset:
Neoadjuvant mFOLFIRINOX vs mFOLFIRINOX Plus Radiotherapy in Patients With Borderline Resectable Pancreatic Cancer—The A021501 Trial
Authors: Neris Dincer, Gamze Ugurluer, Enis Ozyar
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases
Authors: Nancy U. Lin, Rashmi K. Murthy, Vandana Abramson, Carey Anders, Thomas Bachelot, Philippe L. Bedard, Virginia Borges, David Cameron, Lisa A. Carey, A. Jo Chien, Giuseppe Curigliano, Michael P. DiGiovanna, Karen Gelmon, Gabriel Hortobagyi, Sara A. Hurvitz, Ian Krop, Sherene Loi, Sibylle Loibl, Volkmar Mueller, Mafalda Oliveira, Elisavet Paplomata, Mark Pegram, Dennis Slamon, Amelia Zelnak, Jorge Ramos, Wentao Feng, Eric Winer
Journal: JAMA Oncology (2022)

It is estimated that up to 50% of patients with ERBB2 (HER2)-positive metastatic breast cancer (MBC) will develop brain metastases (BMs), which is associated with poor prognosis. Previous reports of the HER2CLIMB trial have demonstrated that tucatinib in combination with trastuzumab and capecitabine provides survival and intracranial benefits for patients with ERBB2-positive MBC and BMs.
Advances in Lipid‐Based Codelivery Systems for Cancer and Inflammatory Diseases
Authors: Chinmay M. Jogdeo, Sudipta Panja, Shrey Kanvinde, Ekta Kapoor, Kasturi Siddhanta, David Oupický
Journal: Advanced Healthcare Materials (2022)

Combination therapy targeting multiple therapeutic targets is a favorable strategy to achieve better therapeutic outcomes in cancer and inflammatory diseases. Codelivery is a subfield of drug delivery that aims to achieve combined delivery of diverse therapeutic cargoes within the same delivery system, thereby ensuring delivery to the same site and providing an opportunity to tailor the release kinetics as desired. Among the wide range of materials being investigated in the design of codelivery systems, lipids have stood out on account of their low toxicity, biocompatibility, and ease of formulation scale-up. This review highlights the advances of the last decade in lipid-based codelivery systems focusing on the codelivery of drug-drug, drug-nucleic acid, nucleic acid-nucleic acid, and protein therapeutic-based combinations for targeted therapy in cancer and inflammatory diseases.
The Fresh Assault on Insurance Coverage Mandates
Authors: Michelle M. Mello, Anne Joseph O’Connell
Journal: New England Journal of Medicine (2022)

Interview with Prof. Michelle Mello on Braidwood Management Inc. v. Becerra and its potential implications. (10:57)Download Braidwood Management Inc. v. Becerra targets the ACA's use of USPSTF recommendations as a basis for mandating insurance coverage for preventive care and threatens access to important health services.
Gallium-68–labeled Peptide PET Quantifies Tumor Exposure of PD-L1 Therapeutics
Authors: Akhilesh Mishra, Dhiraj Kumar, Kuldeep Gupta, Gabriela Lofland, Ajay Kumar Sharma, Dhanush S. Banka, Robert F. Hobbs, Robert F. Dannals, Steven P. Rowe, Edward Gabrielson, Sridhar Nimmagadda
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Immune checkpoint therapy (ICT) is currently ineffective in a majority of patients. Tumor drug exposure measurements can provide vital insights into mechanisms involved in the resistance of solid tumors to those therapeutics; however, tools to quantify in situ drug exposure are few. We have investigated the potential of programmed death-ligand 1 (PD-L1) pharmacodynamics, quantified using PET, to inform on the tumor exposure of anti–PD-L1 (aPD-L1) therapeutics. Experimental Design: To noninvasively quantify PD-L1 levels, we first developed a novel peptide-based gallium-68–labeled binder, [68Ga]Ga-DK223, and evaluated its in vivo distribution, pharmacokinetics, and PD-L1 specificity in preclinical models of triple-negative breast cancer and urothelial carcinoma with variable PD-L1 expression. We then quantified baseline and accessible PD-L1 levels in tumors as a noninvasive pharmacodynamic measure to assess tumor exposure to two aPD-L1 antibodies (avelumab and durvalumab). Results: DK223 exhibited a KD of 1.01±0.83 nmol/L for PD-L1 and inhibited the PD-1:PD-L1 interaction in a dose-dependent manner. [68Ga]Ga-DK223 provides high-contrast PET images within 60 minutes of administration and detects PD-L1 in an expression-dependent manner in xenograft models. PD-L1 pharmacodynamics measured using [68Ga]Ga-DK223-PET revealed that avelumab and durvalumab had similar exposure early during therapy, but only durvalumab exhibited sustained exposure at the tumor. Conclusions: [68Ga]Ga-DK223 detected variable PD-L1 levels and exhibited salient features required for clinical translation. [68Ga]Ga-DK223-PET could be useful for quantifying total PD-L1 levels at baseline and accessible PD-L1 levels during therapy to understand drug exposure at the tumor, thus supporting its use for guiding and optimizing ICT.
Dynamic Mutational Landscape of Cerebrospinal Fluid Circulating Tumor DNA and Predictors of Survival after Proton Craniospinal Irradiation for Leptomeningeal Metastases
Authors: N. Ari Wijetunga, Alexander G. Goglia, Nils Weinhold, Michael F. Berger, Michael Cislo, Daniel S. Higginson, Kiana Chabot, Ahmed M. Osman, Lauren Schaff, Elena Pentsova, Alexandra M. Miller, Simon N. Powell, Adrienne Boire, Jonathan T. Yang
Journal: Clinical Cancer Research (2022)

Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response.We subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel. In parallel, plasma ctDNA and primary tumors were subjected to targeted sequencing. Variant allele frequency (VAF) and cancer cell fraction (CCF) were calculated; clonality of observed mutations was determined. Kaplan-Meier analysis was used to associate genomic changes with survival.The median overall survival (OS) for the cohort was 9 months [interquartile range (IQR), 5-21 months]. We showed clonal evolution between tumor and ctDNA of the CSF and plasma with unique mutations identified by compartment. Higher CSF ctDNA mean VAF before pCSI (VAFpre) had worse OS (6 months for VAFpre ≥ 0.32 vs. 9 months for VAFpre < 0.32; P = 0.05). Similarly, increased VAF after pCSI portended worse survival (6 vs. 18 months; P = 0.008). Higher mean CCF of subclonal mutations appearing after pCSI was associated with worse OS (8 vs. 17 months; P = 0.05).In patients with solid tumor LM undergoing pCSI, we found unique genomic profiles associated with pCSI through CSF ctDNA analyses. Patients with reduced genomic diversity within the leptomeningeal compartment demonstrated improved OS after pCSI suggesting that CSF ctDNA analysis may have use in predicting pCSI response.
Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults
Authors: Rajesh T. Gandhi, Roger Bedimo, Jennifer F. Hoy, Raphael J. Landovitz, Davey M. Smith, Ellen F. Eaton, Clara Lehmann, Sandra A. Springer, Paul E. Sax, Melanie A. Thompson, Constance A. Benson, Susan P. Buchbinder, Carlos del Rio, Joseph J. Eron, Huldrych F. Günthard, Jean-Michel Molina, Donna M. Jacobsen, Michael S. Saag
Journal: JAMA (2022)

Recent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice.Based on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection.A panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered.Initiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor-containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential.Advances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.
Neoadjuvant mFOLFIRINOX vs mFOLFIRINOX Plus Radiotherapy in Patients With Borderline Resectable Pancreatic Cancer—The A021501 Trial
Authors: Aaron J. Grossberg, Krishan R. Jethwa, Susannah G. Ellsworth
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Neoadjuvant mFOLFIRINOX vs mFOLFIRINOX Plus Radiotherapy in Patients With Borderline Resectable Pancreatic Cancer—The A021501 Trial—Reply
Authors: Matthew H. G. Katz, Joseph M. Herman, Eileen M. O’Reilly
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Synthetic Biology in the Engineering of CAR-T and CAR-NK Cell Therapies: Facts and Hopes
Authors: Justin D. Clubb, Torahito A. Gao, Yvonne Y. Chen
Journal: Clinical Cancer Research (2022)

Abstract The advent of modern synthetic-biology tools has enabled the development of cellular treatments with engineered specificity, leading to a new paradigm in anticancer immunotherapy. T cells have been at the forefront of such development, with six chimeric antigen receptor–modified T-cell products approved by the FDA for the treatment of hematologic malignancies in the last 5 years. Natural killer (NK) cells are innate lymphocytes with potent cytotoxic activities, and they have become an increasingly attractive alternative to T-cell therapies due to their potential for allogeneic, “off-the-shelf” applications. However, both T cells and NK cells face numerous challenges, including antigen escape, the immunosuppressive tumor microenvironment, and potential for severe toxicity. Many synthetic-biology strategies have been developed to address these obstacles, most commonly in the T-cell context. In this review, we discuss the array of strategies developed to date, their application in the NK-cell context, as well as opportunities and challenges for clinical translation.
Deep problems with neural network models of human vision
Authors: Jeffrey S. Bowers, Gaurav Malhotra, Marin Dujmović, Milton Llera Montero, Christian Tsvetkov, Valerio Biscione, Guillermo Puebla, Federico Adolfi, John E. Hummel, Rachel F. Heaton, Benjamin D. Evans, Jeffrey Mitchell, Ryan Blything
Journal: Behavioral and Brain Sciences (2022)

Abstract Deep neural networks (DNNs) have had extraordinary successes in classifying photographic images of objects and are often described as the best models of biological vision. This conclusion is largely based on three sets of findings: (1) DNNs are more accurate than any other model in classifying images taken from various datasets, (2) DNNs do the best job in predicting the pattern of human errors in classifying objects taken from various behavioral datasets, and (3) DNNs do the best job in predicting brain signals in response to images taken from various brain datasets (e.g., single cell responses or fMRI data). However, these behavioral and brain datasets do not test hypotheses regarding what features are contributing to good predictions and we show that the predictions may be mediated by DNNs that share little overlap with biological vision. More problematically, we show that DNNs account for almost no results from psychological research. This contradicts the common claim that DNNs are good, let alone the best, models of human object recognition. We argue that theorists interested in developing biologically plausible models of human vision need to direct their attention to explaining psychological findings. More generally, theorists need to build models that explain the results of experiments that manipulate independent variables designed to test hypotheses rather than compete on making the best predictions. We conclude by briefly summarizing various promising modeling approaches that focus on psychological data.
Survival Outcomes, Digital TILs, and On-treatment PET/CT During Neoadjuvant Therapy for HER2-positive Breast Cancer: Results from the Randomized PREDIX HER2 Trial
Authors: Alexios Matikas, Hemming Johansson, Per Grybäck, Judith Bjöhle, Balazs Acs, Ceren Boyaci, Tobias Lekberg, Hanna Fredholm, Ellinor Elinder, Sara Margolin, Erika Isaksson-Friman, Ana Bosch, Henrik Lindman, Jamila Adra, Anne Andersson, Susanne Agartz, Mats Hellström, Ioannis Zerdes, Johan Hartman, Jonas Bergh, Thomas Hatschek, Theodoros Foukakis
Journal: Clinical Cancer Research (2022)

Abstract Purpose: PREDIX HER2 is a randomized Phase II trial that compared neoadjuvant docetaxel, trastuzumab, and pertuzumab (THP) with trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Rates of pathologic complete response (pCR) did not differ between the two groups. Here, we present the survival outcomes from PREDIX HER2 and investigate metabolic response and tumor-infiltrating lymphocytes (TIL) as prognostic factors. Patients and Methods: In total, 202 patients with HER2-positive breast cancer were enrolled and 197 patients received six cycles of either THP or T-DM1. Secondary endpoints included event-free survival (EFS), recurrence-free survival (RFS), and overall survival (OS). Assessment with PET/CT was performed at baseline, after two and six treatment cycles. TILs were assessed manually at baseline biopsies, while image-based evaluation of TILs [digital TILs (DTIL)] was performed in digitized full-face sections. Results: After a median follow-up of 5.21 years, there was no difference between the two treatment groups in terms of EFS [HR = 1.26; 95% confidence interval (CI), 0.54–2.91], RFS (HR = 0.69; 95% CI, 0.24–1.93), or OS (HR = 0.52; 95% CI, 0.09–2.82). Higher SUVmax at cycle 2 (C2) predicted lower pCR (ORadj = 0.65; 95% CI, 0.48–0.87; P = 0.005) and worse EFS (HRadj = 1.27; 95% CI, 1.12–1.41; P &amp;lt; 0.001). Baseline TILs and DTILs provided additional prognostic information to clinical parameters and C2 SUVmax. Conclusions: Long-term outcomes following neoadjuvant T-DM1 were similar to neoadjuvant THP. SUVmax after two cycles of neoadjuvant therapy for HER2-positive breast cancer may be an independent predictor of both short- and long-term outcomes. Combined assessment with TILs may facilitate early selection of poor responders for alternative treatment strategies.
Neoadjuvant mFOLFIRINOX vs mFOLFIRINOX Plus Radiotherapy in Patients With Borderline Resectable Pancreatic Cancer—The A021501 Trial
Authors: Brace Hintz, Vincent J. Lee
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Reemergence of Cholera in Haiti
Authors: Daniel H F Rubin, Franz G Zingl, Deborah R Leitner, Ralph Ternier, Valusnor Compere, Samson Marseille, Damien Slater, Jason B Harris, Fahima Chowdhury, Firdausi Qadri, Jacques Boncy, Louise C Ivers, Matthew K Waldor
Journal: New England Journal of Medicine (2022)

Reemergence of Cholera in HaitiTo the Editor: Cholera was absent from Haiti until an inadvertent introduction by United Nations security forces in October 2010.The ensuing epidemic sickened 820,000 people and caused 9792 reported deaths. 1 The last confirmed cholera case in Haiti was recorded in January 2019, and in February 2022, cholera was declared to have been eliminated in Haiti. 2 In late September 2022, a new outbreak began in Port-au-Prince and rapidly expanded to include 11,953 suspected cases by late November, more than 1000 of which were confirmed by culture. 3We conducted a genomic and phenotypic analysis of the Vibrio cholerae isolated from a stool specimen obtained on September 30, 2022, from an index patient -a child who presented with watery diarrhea and severe dehydration -to begin to address the origins of the epidemic.The 2022 V. cholerae isolate shares phenotypes with the 2010 outbreak strain.Both strains are V. cholerae serogroup O1 (El Tor biotype) of the Ogawa serotype and have similar antimicrobial resistance profiles, including resistance to trimethoprim-sulfamethoxazole and low-level resistance to ciprofloxacin (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).This resistance profile is consistent among 130 isolates from the current outbreak, which suggests that the strain that was isolated from the index patient is representative of the ongoing epidemic.To decipher the relationship between the current outbreak strain and other toxigenic O1 El Tor strains from the ongoing seventh pandemic of cholera, we sequenced the isolate obtained on September 30, 2022, along with four isolates obtained in 2021 and 2022 from Dhaka, Bangladesh (Table S2).Phylogenetic analysis of more than 1200 isolates revealed that the 2022 Haiti